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1.
Nat Immunol ; 24(10): 1725-1734, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37735591

RESUMEN

The immune response to SARS-CoV-2 antigen after infection or vaccination is defined by the durable production of antibodies and T cells. Population-based monitoring typically focuses on antibody titer, but there is a need for improved characterization and quantification of T cell responses. Here, we used multimodal sequencing technologies to perform a longitudinal analysis of circulating human leukocytes collected before and after immunization with the mRNA vaccine BNT162b2. Our data indicated distinct subpopulations of CD8+ T cells, which reliably appeared 28 days after prime vaccination. Using a suite of cross-modality integration tools, we defined their transcriptome, accessible chromatin landscape and immunophenotype, and we identified unique biomarkers within each modality. We further showed that this vaccine-induced population was SARS-CoV-2 antigen-specific and capable of rapid clonal expansion. Moreover, we identified these CD8+ T cell populations in scRNA-seq datasets from COVID-19 patients and found that their relative frequency and differentiation outcomes were predictive of subsequent clinical outcomes.


Asunto(s)
Linfocitos T CD8-positivos , COVID-19 , Humanos , Vacunas contra la COVID-19 , SARS-CoV-2 , Vacuna BNT162 , COVID-19/prevención & control , Vacunación , Anticuerpos Antivirales
2.
Bioscience ; 74(3): 146-158, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38560618

RESUMEN

What are social niches, and how do they arise and change? Our first goal in the present article is to clarify the concept of an individualized social niche and to distinguish it from related concepts, such as a social environment and a social role. We argue that focal individuals are integral parts of individualized social niches and that social interactions with conspecifics are further core elements of social niches. Our second goal in the present article is to characterize three types of processes-social niche construction, conformance, and choice (social NC3 processes)-that explain how individualized social niches originate and change. Our approach brings together studies of behavior, ecology, and evolution and integrates social niches into the broader concept of an individualized ecological niche. We show how clarifying the concept of a social niche and recognizing the differences between the three social NC3 processes enhance and stimulate empirical research.

3.
Health Care Anal ; 32(2): 141-164, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38285121

RESUMEN

The term 'environment' is not uniformly defined in the public health sciences, which causes crucial inconsistencies in research, health policy, and practice. As we shall indicate, this is somewhat entangled with diverging pathogenic and salutogenic perspectives (research and policy priorities) concerning environmental health. We emphasise two distinct concepts of environment in use by the World Health Organisation. One significant way these concepts differ concerns whether the social environment is included. Divergence on this matter has profound consequences for the understanding of health and disease, for measures derived from that understanding targeting health promotion and disease prevention, and consequently, for epistemic structures and concept development in scientific practice. We hope to improve the given situation in public health by uncovering these differences and by developing a fruitful way of thinking about environment. Firstly, we side with the salutogenic conception of environment as a health resource (as well as a source of health risks). Secondly, we subdivide the concept of environment into four health-oriented environmental categories (viz., natural, built-material, socio-cultural, and psychosocial) and we link these with other theoretical notions proposed in the health sciences literature. Thirdly, we propose that in public health 'environment' should be understood as consisting of all extrinsic factors that influence or are influenced by the health, well-being, and development of an individual. Consequently, none of the four categories should be excluded from the concept of environment. We point out the practical relevance and fruitfulness of the conception of environment as a health source and frame this in causal terms, representing individual health environments as causal networks. Throughout, we side with the view that for the design of human health-promoting settings, increased attention and consideration of environmental resources of salutogenic potential is particularly pressing.


Asunto(s)
Salud Pública , Humanos , Medio Social , Ambiente , Salud Ambiental , Política de Salud , Promoción de la Salud
4.
Genome Res ; 30(12): 1781-1788, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33093069

RESUMEN

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 864 SARS-CoV-2 sequences from cases in the New York City metropolitan area during the COVID-19 outbreak in spring 2020. The majority of cases had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that early transmission was most linked to cases from Europe. Our data are consistent with numerous seeds from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of genomic surveillance in addition to traditional epidemiological indicators.


Asunto(s)
COVID-19 , Genoma Viral , Pandemias , Filogenia , SARS-CoV-2/genética , Secuenciación Completa del Genoma , COVID-19/epidemiología , COVID-19/genética , COVID-19/transmisión , Femenino , Humanos , Masculino , Ciudad de Nueva York
5.
Ann Neurol ; 91(6): 782-795, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35289960

RESUMEN

OBJECTIVE: The objective of this study was to determine the impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on the development of cellular and humoral immunity to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. METHODS: Patients with MS aged 18 to 60 years were evaluated for anti-nucleocapsid and anti-Spike receptor-binding domain (RBD) antibody with electro-chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N-terminal domain with multiepitope bead-based immunoassays (MBI); live virus immunofluorescence-based microneutralization assay; T-cell responses to SARS-CoV-2 Spike using TruCulture enzyme-linked immunosorbent assay (ELISA); and IL-2 and IFNγ ELISpot assays. Assay results were compared by DMT class. Spearman correlation and multivariate analyses were performed to examine associations between immunologic responses and infection severity. RESULTS: Between January 6, 2021, and July 21, 2021, 389 patients with MS were recruited (mean age 40.3 years; 74% women; 62% non-White). Most common DMTs were ocrelizumab (OCR)-40%; natalizumab -17%, Sphingosine 1-phosphate receptor (S1P) modulators -12%; and 15% untreated. One hundred seventy-seven patients (46%) had laboratory evidence of SARS-CoV-2 infection; 130 had symptomatic infection, and 47 were asymptomatic. Antibody responses were markedly attenuated in OCR compared with other groups (p ≤0.0001). T-cell responses (IFNγ) were decreased in S1P (p = 0.03), increased in natalizumab (p <0.001), and similar in other DMTs, including OCR. Cellular and humoral responses were moderately correlated in both OCR (r = 0.45, p = 0.0002) and non-OCR (r = 0.64, p <0.0001). Immune responses did not differ by race/ethnicity. Coronavirus disease 2019 (COVID-19) clinical course was mostly non-severe and similar across DMTs; 7% (9/130) were hospitalized. INTERPRETATION: DMTs had differential effects on humoral and cellular immune responses to SARS-CoV-2 infection. Immune responses did not correlate with COVID-19 clinical severity in this relatively young and nondisabled group of patients with MS. ANN NEUROL 2022;91:782-795.


Asunto(s)
COVID-19 , Esclerosis Múltiple , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Antivirales , Etnicidad , Femenino , Humanos , Inmunidad Celular , Inmunidad Humoral , Masculino , Natalizumab/uso terapéutico , SARS-CoV-2
6.
Transpl Infect Dis ; 25(6): e14122, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37707287

RESUMEN

BACKGROUND: Understanding immunogenicity and alloimmune risk following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in kidney transplant recipients is imperative to understanding the correlates of protection and to inform clinical guidelines. METHODS: We studied 50 kidney transplant recipients following SARS-CoV-2 vaccination and quantified their anti-spike protein antibody, donor-derived cell-free DNA (dd-cfDNA), gene expression profiling (GEP), and alloantibody formation. RESULTS: Participants were stratified using nucleocapsid testing as either SARS-CoV-2-naïve or experienced prior to vaccination. One of 34 (3%) SARS-CoV-2 naïve participants developed anti-spike protein antibodies. In contrast, the odds ratio for the association of a prior history of SARS-CoV-2 infection with vaccine response was 18.3 (95% confidence interval 3.2, 105.0, p < 0.01). Pre- and post-vaccination levels did not change for median dd-cfDNA (0.23% vs. 0.21% respectively, p = 0.13), GEP scores (9.85 vs. 10.4 respectively, p = 0.45), calculated panel reactive antibody, de-novo donor specific antibody status, or estimated glomerular filtration rate. CONCLUSIONS: SARS-CoV-2 vaccines do not appear to trigger alloimmunity in kidney transplant recipients. The degree of vaccine immunogenicity was associated most strongly with a prior history of SARS-CoV-2 infection.


Asunto(s)
COVID-19 , Ácidos Nucleicos Libres de Células , Trasplante de Riñón , Humanos , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Inmunidad , SARS-CoV-2 , Receptores de Trasplantes , Vacunación
7.
Mol Cell ; 57(6): 984-994, 2015 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-25728768

RESUMEN

One of several roles of the Mycobacterium tuberculosis proteasome is to defend against host-produced nitric oxide (NO), a free radical that can damage numerous biological macromolecules. Mutations that inactivate proteasomal degradation in Mycobacterium tuberculosis result in bacteria that are hypersensitive to NO and attenuated for growth in vivo, but it was not known why. To elucidate the link between proteasome function, NO resistance, and pathogenesis, we screened for suppressors of NO hypersensitivity in a mycobacterial proteasome ATPase mutant and identified mutations in Rv1205. We determined that Rv1205 encodes a pupylated proteasome substrate. Rv1205 is a homolog of the plant enzyme LONELY GUY, which catalyzes the production of hormones called cytokinins. Remarkably, we report that an obligate human pathogen secretes several cytokinins. Finally, we determined that the Rv1205-dependent accumulation of cytokinin breakdown products is likely responsible for the sensitization of Mycobacterium tuberculosis proteasome-associated mutants to NO.


Asunto(s)
Aminohidrolasas/metabolismo , Citocininas/biosíntesis , Mycobacterium tuberculosis/metabolismo , Óxido Nítrico/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Aldehídos/metabolismo , Aminohidrolasas/genética , Animales , Proteínas de Arabidopsis/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Citocininas/metabolismo , Interacciones Huésped-Patógeno , Ratones Endogámicos C57BL , Mutación , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidad , Óxido Nítrico/farmacología , Supresión Genética
8.
Nord J Psychiatry ; 77(5): 440-446, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36344233

RESUMEN

OBJECTIVE: Electroconvulsive therapy (ECT) en bloc is defined as ECT administered on 2-3 consecutive days. In Denmark, ECT en bloc is recommended for severe conditions such as catatonia, treatment-resistant mania/psychosis, or imminent risk of suicide. To our knowledge, there are no recent reports on the use of ECT en bloc in clinical practice. Here, we provide such a report. METHODS: We characterized the use of ECT en bloc in the period from 2006-2019 based on data from Danish national registers. Furthermore, we compared mortality rates between patients receiving ECT en bloc and patients receiving standard regimen ECT (not en bloc). RESULTS: We identified 2173 patients who received a total of 2734 ECT en bloc treatment courses in Denmark in the period from 2006 to 2019 (6% of the total number of ECT treatment courses). The use of ECT en bloc was stable over the study period (range: 138-196 patients per year). The most common treatment indications were unipolar depression (41%), psychotic disorder (23%), and bipolar disorder (20%). The vast majority (90%) received ECT en bloc voluntarily. The 1-year mortality rate ratio for ECT en bloc compared to standard regimen ECT was 1.42 (95%CI: 1.03-1.95). CONCLUSION: The use of ECT en bloc in Denmark is stable both in terms of the number of patients treated and treatment indications. In keeping with ECT en bloc being used for severe conditions, those receiving this treatment have a higher mortality rate compared to those receiving standard ECT, warranting careful monitoring during follow-up.


Asunto(s)
Trastorno Bipolar , Trastorno Depresivo , Terapia Electroconvulsiva , Trastornos Psicóticos , Humanos , Terapia Electroconvulsiva/efectos adversos , Trastorno Bipolar/terapia , Trastornos Psicóticos/terapia , Trastorno Depresivo/terapia , Dinamarca/epidemiología , Resultado del Tratamiento
9.
Comput Inform Nurs ; 41(9): 706-716, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-36749849

RESUMEN

The use of symptom management mobile apps can reduce patients' symptom burden during cancer treatment, but the evidence is lacking about their effect on care. Moreover, if patients' health literacy can be improved, it needs to be more rigorously tested. This study aimed to evaluate patients' perceptions of individualized care and health literacy using an interactive app in two randomized trials. Patients undergoing neoadjuvant chemotherapy for breast cancer (N = 149) and radiotherapy for prostate cancer (N = 150) were consecutively included and randomized into one intervention or control group. Outcome measures were Individualized Care Scale, Swedish Functional Health Literacy Scale, and Swedish Communicative and Critical Health Literacy Scale. In the breast cancer trial, no group differences were observed regarding individualized care or health literacy. Most patients had sufficient health literacy levels. In the prostate cancer trial, intervention group patients rated higher perceived individualized care regarding decision control at follow-up than the control group. Less than half had sufficient health literacy levels and intervention group patients significantly improved their ability to seek, understand, and communicate health information. Education level explained significant variance in health literacy in both trials. Using an interactive app can positively affect individualization in care and health literacy skills among patients treated for prostate cancer, although further research is warranted.


Asunto(s)
Neoplasias de la Mama , Alfabetización en Salud , Aplicaciones Móviles , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Mama/terapia , Neoplasias de la Próstata/terapia , Femenino
10.
Arch Orthop Trauma Surg ; 143(5): 2503-2507, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35657414

RESUMEN

INTRODUCTION: Posterior shoulder dislocation in association with reverse Hill-Sachs lesion is a rather rare injury. Few studies reporting results after joint-preserving surgery in these cases are available. This current study presents the clinical outcomes 10 years postoperatively. MATERIALS AND METHODS: In a prospective case series, we operatively treated 12 consecutive patients (all males) after posterior shoulder dislocation with associated reverse Hill-Sachs lesion using joint-preserving techniques. Patients received surgery in a single center between January 2008 and December 2011. The joint-preserving surgical procedure was chosen depending on the defect size and bone quality. The following outcome-measures were analyzed: Constant-Score, DASH-Score, ROWE-Score, and SF-12. Results 1, 5, and 10 years postoperatively were compared. RESULTS: Out of 12 patients, ten patients (83.3%) were followed-up with a mean follow-up interval of 10.7 years (range 9.3-12.8). The mean patient age at the time of the last follow-up was 51 years (32-66). The outcome scores at the final follow-up were: Constant 92.5 (range 70.0-100), DASH 3.2 (0.0-10.8), ROWE 91.0 (85.0-100), and SF-12 87.8 (77.5-98.3). Clinical results had improved from 1 to 5 years postoperatively and showed a tendency for even further improvement after 10 years. CONCLUSIONS: Joint-preserving surgical therapy of posterior shoulder dislocation provides excellent results when the morphology of the reverse Hill-Sachs lesion is respected in surgical decision-making. TRIAL REGISTRATION: 223/2012BO2, 02 August 2010.


Asunto(s)
Lesiones de Bankart , Enfermedades Óseas , Inestabilidad de la Articulación , Luxación del Hombro , Articulación del Hombro , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Luxación del Hombro/cirugía , Luxación del Hombro/complicaciones , Lesiones de Bankart/cirugía , Enfermedades Óseas/complicaciones , Evaluación de Resultado en la Atención de Salud , Inestabilidad de la Articulación/cirugía , Articulación del Hombro/cirugía , Recurrencia
11.
Bioscience ; 72(6): 538-548, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35677293

RESUMEN

Organisms interact with their environments in various ways. We present a conceptual framework that distinguishes three mechanisms of organism-environment interaction. We call these NC3 mechanisms: niche construction, in which individuals make changes to the environment; niche choice, in which individuals select an environment; and niche conformance, in which individuals adjust their phenotypes in response to the environment. Each of these individual-level mechanisms affects an individual's phenotype-environment match, its fitness, and its individualized niche, defined in terms of the environmental conditions under which the individual can survive and reproduce. Our framework identifies how individuals alter the selective regimes that they and other organisms experience. It also places clear emphasis on individual differences and construes niche construction and other processes as evolved mechanisms. The NC3 mechanism framework therefore helps to integrate population-level and individual-level research.

12.
Arch Sex Behav ; 51(6): 3035-3048, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35876980

RESUMEN

Compersion refers to the positive feelings, such as joy, excitement and contentment, that one may experience in response to one's partner's other consensually non-monogamous (CNM) intimate relationship(s). In the study, we recruited 44 CNM participants who had experienced compersion to complete an open-ended online survey regarding the factors that facilitated and hindered their experiences of compersion. A thematic analysis identified three main themes: intrapersonal/individual factors, experiences in and characteristics of the relationship with one's partner(s), and feelings/judgments about one's metamour (one's partner's partner). The factors most commonly named by participants as facilitating compersion included: feelings of self-worth, feeling secure and that one's needs were being met in the relationship with the partner, communication with one's partner, and positive regard for one's metamour. Participants shared conflicting experiences regarding the nature of the relationship between jealousy and compersion and whether the ability to feel compersion was innate or learned. Findings were generally consistent with the small body of literature on this phenomenon. Several theories, including Broaden-and-Build, Self-Expansion, and Crossover, may help us understand the underpinnings of compersion and the pathways through which the experience might strengthen and deepen relationships. The study's results suggest multiple hypotheses ripe for future testing. Increasing our knowledge of this little known phenomenon carries the potential to help us identify strategies to manage jealousy and increase positive feelings across all relationship types.


Asunto(s)
Conducta Sexual , Parejas Sexuales , Humanos , Celos , Matrimonio , Encuestas y Cuestionarios
14.
J Bacteriol ; 201(19)2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31285241

RESUMEN

The cell envelope of Mycobacterium tuberculosis is a key target for antibiotics, yet its assembly and maintenance remain incompletely understood. Here we report that Rv2700, a previously uncharacterized M. tuberculosis gene, contributes to envelope integrity. Specifically, an Rv2700 mutant strain had a decreased growth rate, increased sensitivity to antibiotics that target peptidoglycan crosslinking, and increased cell envelope permeability. We propose that Rv2700 be named a "cell envelope integrity" gene (cei). Importantly, a cei mutant had attenuated virulence in mice. Cei shares predicted structural homology with another M. tuberculosis protein, VirR (Rv0431), and we found that a virR mutant had growth rate, antibiotic sensitivity, and envelope permeability phenotypes similar to those of the cei mutant. Both Cei and VirR are predicted to consist of a transmembrane helix and an extracellular LytR_C domain. LytR_C domains have no known function, but they are also found in a family of proteins, the LytR-Cps2A-Psr (LCP) enzymes, that perform important cell envelope functions in a range of bacteria. In mycobacteria, LCP enzymes attach arabinogalactan to peptidoglycan, and mycobacterial LCP enzyme mutants have phenotypes similar to those of virR- and cei-deficient strains. Collectively, our results suggest that LytR_C domain proteins may contribute to the cell envelope functions performed by LCP proteins. This study provides a framework for further mechanistic investigations of LytR_C proteins and, more broadly, for advancing our understanding of the cell envelopes of mycobacteria and other medically and economically important genera.IMPORTANCEMycobacterium tuberculosis causes about 1.5 million deaths per year. The unique composition of the Mycobacterium tuberculosis cell envelope is required for this bacterium to cause disease and is the target for several critical antibiotics. By better understanding the mechanisms by which mycobacteria assemble and maintain their cell envelope, we might uncover new therapeutic targets. In this work, we show that a previously uncharacterized protein, Rv2700, is important for cell envelope integrity in Mycobacterium tuberculosis and that loss of Rv2700 attenuates virulence in mice. This family of proteins is found in a broad group of bacterial species, so our work provides a first insight into their potential functions in many species important to the environment, industry, and human health.


Asunto(s)
Pared Celular/metabolismo , Mycobacterium tuberculosis/patogenicidad , Tuberculosis/microbiología , Factores de Virulencia/química , Factores de Virulencia/genética , Animales , Antibacterianos/farmacología , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Femenino , Ratones , Viabilidad Microbiana/efectos de los fármacos , Modelos Moleculares , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/inmunología , Permeabilidad , Dominios Proteicos , Homología Estructural de Proteína , Factores de Virulencia/metabolismo
15.
Malar J ; 18(1): 337, 2019 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-31581943

RESUMEN

BACKGROUND: The recent emergence in Southeast Asia of artemisinin resistance poses major threats to malaria control and elimination globally. Green nanotechnologies can constitute interesting tools for discovering anti-malarial medicines. This systematic review focused on the green synthesis of metal nanoparticles as potential source of new antiplasmodial drugs. METHODS: Seven electronic database were used following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 17 papers were included in the systematic review. 82.4% of the studies used plant leaves to produce nanoparticles (NPs) while three studies used microorganisms, including bacteria and fungi. Silver was the main metal precursor for the synthesis of NPs. The majority of studies obtained nanoparticles spherical in shape, with sizes ranging between 4 and 65 nm, and reported no or little cytotoxic effect of the NPs. Results based on 50% inhibitory concentration (IC50) varied between studies but, in general, could be divided into three NP categories; (i) those more effective than positive controls, (ii) those more effective than corresponding plant extracts and, (iii) those less effective than the positive controls or plant extracts. CONCLUSIONS: This study highlights the high antiplasmodial potential of green-synthesized metal nanoparticles thereby underscoring the possibility to find and develop new anti-malarial drugs based on green synthesis approaches. However, the review also highlights the need for extensive in vitro and in vivo studies to confirm their safety in humans and the elucidation of the mechanism of action.


Asunto(s)
Antimaláricos/síntesis química , Descubrimiento de Drogas/tendencias , Nanopartículas del Metal/química , Hojas de la Planta/metabolismo , Plasmodium falciparum/efectos de los fármacos , Artemisininas/farmacología , Malaria/tratamiento farmacológico , Extractos Vegetales/química , Plata
16.
Optom Vis Sci ; 96(3): 221-226, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30801497

RESUMEN

SIGNIFICANCE: Although the clinical appearance of pediatric ocular herpes simplex virus (HSV) is similar in children and adults, there is evidence that stromal disease and recurrences are more common in pediatric patients. Misdiagnosis of these patients is common, and patients can develop corneal scarring and amblyopia. PURPOSE: This case series will review important clinical concepts on pediatric ocular HSV including differences in presentation and current treatment recommendations. CASE REPORTS: Three pediatric patients with HSV keratitis are presented: a 6-year-old girl who was treated for unilateral disease over the course of 3 years, a 7-year-old boy who presented with bilateral disease, and a 3-year-old girl in whom the diagnosis was not apparent initially. All patients were successfully treated with oral acyclovir and topical steroids. One patient was also treated with topical antivirals. CONCLUSIONS: Pediatric HSV keratitis should be considered as a differential diagnosis in pediatric patients who present with keratitis. Accurate diagnosis of these patients is important so that amblyopia does not develop. Pediatric ocular HSV patients can be successfully treated with topical and/or oral medications, although their treatment duration may be 12 months or longer.


Asunto(s)
Queratitis Herpética/diagnóstico , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Queratitis Herpética/tratamiento farmacológico , Masculino , Recurrencia , Agudeza Visual/fisiología
17.
Scand J Caring Sci ; 32(2): 715-724, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29048131

RESUMEN

RATIONALE AND AIM: Most women of working ages with limited breast cancer (BC) have returned to work within the first year after diagnosis. However, little is known about what is happening during this year regarding sickness absence and return to work. Also, the knowledge is very limited about the occurrence of part-time sickness absence after BC diagnosis. Therefore, the aim of this study was to describe occurrence, extent and length of SA during a two-year follow-up after BC surgery and to analyse the association between being SA and type of cancer treatment. METHODS: In this prospective cohort study, 497 women responded to questionnaires about different aspects of sickness absence at six occasions during two years after primary BC surgery (at baseline and after 4, 8, 12, 18 and 24 months). Treatment information was obtained from the National breast cancer register. Multinomial logistic regression was used to calculate odds ratios (OR) for likelihood of being sickness absent more than once. RESULTS: Two-thirds of the women were sickness absent at baseline; this proportion decreased, especially during the first eight months. At 24 months, 13% were sickness absent. Of all women, 27% never reported sickness absence and 14% were sickness absent at most of the six survey times. At eight months, many had shifted from full- to part-time sickness absence. Women with chemotherapy and/or advanced BC surgery had higher ORs for being sickness absent at most of the follow-ups. CONCLUSIONS: Most women returned to work within the first eight months after BC surgery and of those sickness absent after that, most had been part-time sickness absent. Thus, it is important to differentiate between part- and full-time sickness absence in future studies. Special attention should be paid to the impact of chemotherapy and type of surgery on the likelihood of being sickness absent.


Asunto(s)
Neoplasias de la Mama/rehabilitación , Neoplasias de la Mama/cirugía , Reinserción al Trabajo/estadística & datos numéricos , Ausencia por Enfermedad/estadística & datos numéricos , Adulto , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Persona de Mediana Edad , Encuestas y Cuestionarios , Factores de Tiempo
18.
J Bacteriol ; 199(7)2017 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-28096448

RESUMEN

Mycobacterium tuberculosis uses a proteasome to degrade proteins by both ATP-dependent and -independent pathways. While much has been learned about ATP-dependent degradation, relatively little is understood about the ATP-independent pathway, which is controlled by Mycobacterium tuberculosisproteasome accessory factor E (PafE). Recently, we found that a Mycobacterium tuberculosispafE mutant has slowed growth in vitro and is sensitive to killing by heat stress. However, we did not know if these phenotypes were caused by an inability to degrade the PafE-proteasome substrate HspR (heat shock protein repressor), an inability to degrade any damaged or misfolded proteins, or a defect in another protein quality control pathway. To address this question, we characterized pafE suppressor mutants that grew similarly to pafE+ bacteria under normal culture conditions. All but one suppressor mutant analyzed contained mutations that inactivated HspR function, demonstrating that the slowed growth and heat shock sensitivity of a pafE mutant were caused primarily by the inability of the proteasome to degrade HspR.IMPORTANCEMycobacterium tuberculosis encodes a proteasome that is highly similar to eukaryotic proteasomes and is required for virulence. We recently discovered a proteasome cofactor, PafE, which is required for the normal growth, heat shock resistance, and full virulence of M. tuberculosis In this study, we demonstrate that PafE influences this phenotype primarily by promoting the expression of protein chaperone genes that are necessary for surviving proteotoxic stress.


Asunto(s)
Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica/fisiología , Proteínas de Choque Térmico/metabolismo , Mycobacterium tuberculosis/metabolismo , Proteínas Represoras/metabolismo , Proteínas Bacterianas/genética , Proteínas de Choque Térmico/genética , Mutación , Mycobacterium tuberculosis/genética , Proteínas Represoras/genética
19.
Lupus ; 26(12): 1291-1296, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28355985

RESUMEN

Objective To study the outcome of patients with antiphospholipid syndrome (APS) after oral anticoagulant treatment cessation. Methods We performed a retrospective study of patients with APS experiencing cessation of oral anticoagulant and enrolled in a French multicentre observational cohort between January 2014 and January 2016. The main outcome was the occurrence of recurrent thrombotic event after oral anticoagulation cessation. Results Forty four APS patients interrupted oral anticoagulation. The median age was 43 (27-56) years. The median duration of anticoagulation was 21 (9-118) months. Main causes of oral anticoagulant treatment cessation were switch from vitamin K antagonists to aspirin in 15 patients, prolonged disappearance of antiphospholipid antibodies in ten, bleeding complications in nine and a poor therapeutic adherence in six. Eleven (25%) patients developed a recurrent thrombotic event after oral anticoagulation cessation, including three catastrophic APS and one death due to lower limb ischemia. Antihypertensive treatment required at time of oral anticoagulants cessation seems to be an important factor associated with recurrent thrombosis after oral anticoagulant cessation (15.2% in patients with no relapse versus 45.5% in patients with recurrent thrombosis, p = 0.038). Oral anticoagulant treatment was re-started in 18 (40.9%) patients. Conclusion The risk of a new thrombotic event in APS patients who stopped their anticoagulation is high, even in those who showed a long lasting disappearance of antiphospholipid antibodies. Except for the presence of treated hypertension, this study did not find a particular clinical or biological phenotype for APS patients who relapsed after anticoagulation cessation. Any stopping of anticoagulant in such patients should be done with caution.


Asunto(s)
Anticuerpos Antifosfolípidos/inmunología , Anticoagulantes/administración & dosificación , Síndrome Antifosfolípido/tratamiento farmacológico , Trombosis/prevención & control , Administración Oral , Adulto , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Síndrome Antifosfolípido/complicaciones , Aspirina/administración & dosificación , Estudios de Cohortes , Femenino , Francia , Hemorragia/inducido químicamente , Humanos , Cumplimiento de la Medicación , Persona de Mediana Edad , Estudios Retrospectivos , Trombosis/epidemiología , Trombosis/etiología , Factores de Tiempo , Adulto Joven
20.
J Sex Med ; 14(6): 797-803, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28479131

RESUMEN

BACKGROUND: Little is known about the long-term consequences of stroke on sexuality, and studies on how individuals with stroke communicate with health care professionals about information and/or interventions on sexuality are even sparser. AIM: To explore experiences of sexuality 6 years after stroke, including communication with health care professionals concerning sexuality. METHODS: This qualitative study was based on data collected by semistructured interviews with 12 informants 43 to 81 years old 6 years after stroke. Interviews were recorded and transcribed verbatim and thematic analysis was performed. RESULTS: The analysis resulted in the following three themes. Not exclusively negative experiences in sexuality after stroke: Most informants experienced some change in their sexual life from before their stroke. Decreased sexual interest and function were ascribed to decreased sensibility, post-stroke pain, or fatigue. Some informants reported positive changes in sexuality, which were attributed to feelings of increased intimacy. Individual differences and variability on how to handle sexuality after stroke: Different strategies were used to manage unwanted negative changes such as actively trying to adapt by planning time with the partner and decreasing pressure or stress. Open communication about sexuality with one's partner also was described as important. Strikingly, most informants with negative experiences of sexual life attributed these to age or a stage in life and not to the stroke or health issues. Furthermore, they compared themselves with others without stroke but with changes in sexuality, thus achieving a sense of normality. Communication and counseling concerning sexuality-many unmet needs: Experiences of communication with health care professionals varied. Very few informants had received any information or discussed sexuality with health care professionals during the 6 years since the stroke, although such needs were identified by most informants. CLINICAL TRANSLATION: When encountering individuals with previous stroke, there is a need for vigilance concerning individual experiences of stroke on sexuality to avoid under- or overestimating the impact and to raise the subject, which currently might be seldom. STRENGTHS AND LIMITATIONS: Individuals with long-term diverse consequences of stroke and with different sociodemographic backgrounds were interviewed. Because most individuals in the present study had retained functioning, this could decrease transferability to populations with more severe sequelae after stroke. CONCLUSIONS AND IMPLICATIONS: The individuals in the present study had different experiences of sexuality after stroke. The results point to the importance of acknowledging sexual rehabilitation as part of holistic person-centered stroke rehabilitation. Nilsson MI, Fugl-Meyer K, von Koch L, Ytterberg C. Experiences of Sexuality Six Years After Stroke: A Qualitative Study. J Sex Med 2017;14:797-803.


Asunto(s)
Conducta Sexual/fisiología , Conducta Sexual/psicología , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/psicología , Adulto , Anciano , Comunicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Parejas Sexuales/psicología , Factores Socioeconómicos
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